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Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) rarely coexist with systemic thrombotic microangiopathy (TMA).The TMA can be in the form of either hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). This review explores the clinical characteristics, histopathological findings, treatment options, and outcomes in patients presenting as AAV with coexisting HUS/TTP. Methods: We conducted a search on the PubMed database and additional searches from January 1998 to September 2022 using the following terms: "ANCA", "Antineutrophil cytoplasmic antibody", "thrombotic thrombocytopenic purpura", "TTP", "thrombotic microangiopathy", "haemolytic uremic syndrome", and "HUS". We excluded articles that described renal-limited TMA. Two authors independently reviewed the full texts and extracted all critical data from the included case reports. Finally, we included 15 cases for this review. Hematological remission and kidney recovery in the form of independence from dialysis was assessed. Results: The median age of the patients was 61 years and a majority of them were females (66.7%). Myeloperoxidase (MPO)-ANCA positivity (66.67%) was more common than proteinase 3 (PR3)-ANCA positivity (33.33%). All patients had laboratory parameters consistent with systemic TMA (HUS or TTP), and only six (out of 11) cases showed histological features of renal TMA. Ten had crescentic glomerulonephritis, and two had advanced degrees of chronicity in histology. Eighty-six percent of cases had hematological remission, and sixty percent of cases became dialysis-independent after treatment. Conclusion: In conclusion, kidney outcome was worse in patients who manifested both AAV and systemic TMA. A paucity of literature regarding this diagnostic quandary calls for avid reporting of such cases. [ABSTRACT FROM AUTHOR]

This article discusses the outcomes of primary membranous nephropathy (PMN) patients who are refractory to immunosuppressants. PMN is a common cause of adult-onset nephrotic syndrome, and current guidelines recommend immunosuppressive therapy. However, a significant proportion of patients do not respond to initial treatment and require rescue therapy. The article presents a systematic review of 18 observational studies that analyzed different rescue therapies for refractory membranous nephropathy. The findings suggest that rituximab, adrenocorticotrophic hormone, and obinutuzumab show promising results, but there is no clear winner. The choice of treatment should be based on individual patient characteristics and side effect profiles. Further controlled studies are needed to investigate these agents. [Extracted from the article]

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70–80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes. [ABSTRACT FROM AUTHOR]

Primary membranous nephropathy (PMN), an autoimmune disease, is the most common cause of nephrotic syndrome in middle-aged non-diabetic adults. PMN pathophysiology includes Th1/Th2 paradigm. The IL-23/IL-17 pathway is implicated in autoimmune kidney disorders, but no study has examined its relationship with PMN. In several unrelated studies, PMN patients reported to have paradoxical IL-17 levels. This manuscript describes the best possible association of IL-23/IL-17 axis with PMN. Biopsy-proven PMN patients and age, gender-matched healthy controls were enrolled. Serum-PLA2R (Euroimmune, Germany), IL-23 and IL-17 (R&D; USA), was measured using ELISA along with biochemical parameters. Appropriate statistical tools were used for analysis. One hundred eighty-nine PMN patients (mean age 41.70 ± 12.53 years) and 100 controls (mean age 43.92 ± 10.93 years) were identified. One hundred forty were PLA2R-related. PMN patients had median proteinuria, serum albumin, and creatinine of 6.12 (3.875, 9.23) g/day, 2.32 (1.96, 2.9) g/dl, and 0.89 (0.7, 1.1) mg/dl, respectively. IL-17, but not IL-23, was significantly increased in PMN patients compared to controls (IL-17, median: 12.07 pg/ml (9.75, 24.56) vs median: 9.75 pg/ml (8.23, 17.03) p = 0.0002); (IL23, median: 6.04 pg/ml (4.22, 10.82) vs median: 5.46 pg/ml (3.34, 9.96) p = 0.142). IL-17 and IL-23 correlated significantly (p 0.05) in PMN patients, and similar trend was seen when grouped into PLA2R-related and -unrelated groups. The levels of IL-23 (p = 0.057) and IL-17 (p = 0.004) were high in MN patients that did not respond to the treatment. The current finding may indicate or suggest the involvement of IL-23/IL-17 PMN pathogenesis. A comprehensive investigation is needed to evaluate IL-23/IL-17 axis with renal infiltrating immune cells, and external stimuli. [ABSTRACT FROM AUTHOR]